Mitochondrial Dysfunction-Evoked DHODH Acetylation is Involved in Renal Cell Ferroptosis during Cisplatin-Induced Acute Kidney Injury.

Several studies have observed renal cell ferroptosis during cisplatin-induced acute kidney injury (AKI). However, the mechanism is not completely clear. In this study, oxidized arachidonic acid (AA) metabolites are increased in cisplatin-treated HK-2 cells. Targeted metabolomics showed that the end product of pyrimidine biosynthesis is decreased and the initiating substrate of pyrimidine biosynthesis is increased in cisplatin-treated mouse kidneys. Mitochondrial DHODH, a key enzyme for pyrimidine synthesis, and its downstream product CoQH2, are downregulated. DHODH overexpression attenuated but DHODH silence exacerbated cisplatin-induced CoQH2 depletion and lipid peroxidation. Mechanistically, renal DHODH acetylation is elevated in cisplatin-exposed mice. Mitochondrial SIRT3 is reduced in cisplatin-treated mouse kidneys and HK-2 cells. Both in vitro SIRT3 overexpression and in vivo NMN supplementation attenuated cisplatin-induced mitochondrial DHODH acetylation and renal cell ferroptosis. By contrast, Sirt3 knockout aggravated cisplatin-induced mitochondrial DHODH acetylation and renal cell ferroptosis, which can not be attenuated by NMN. Additional experiments showed that cisplatin caused mitochondrial dysfunction and SIRT3 SUMOylation. Pretreatment with mitochondria-target antioxidant MitoQ alleviated cisplatin-caused mitochondrial dysfunction, SIRT3 SUMOylation, and DHODH acetylation. MitoQ pretreatment protected against cisplatin-caused AKI and renal cell ferroptosis. Taken together, these results suggest that mitochondrial dysfunction-evoked DHODH acetylation partially contributes to renal cell ferroptosis during cisplatin-induced AKI.

Pyroptosis and its role in autoimmune skin disease.

Autoimmune skin disease is a kind of heterogeneous disease with complicated pathogenesis. Many factors such as genetic, infectious, environmental and even psychological factors may interact together to trigger a synergistic effect for the development of abnormal innate and adaptive immune responses. Although the exact mechanisms remain unclear, recent evidence suggests that pyroptosis plays a pivotal role in the development of autoimmune skin disease. The feature of pyroptosis is the first formation of pores in cellular membranes, then cell rupture and the release of intracellular substances and pro-inflammatory cytokines, such as interleukin-1 beta (IL-1ß) and IL-18. This hyperactive inflammatory programmed cell death damages the homeostasis of the immune system and advances autoimmunity. This review briefly summarises the molecular regulatory mechanisms of pyrin domain-containing protein 3 (NLRP3) inflammasome and gasdermin family, as well as the molecular mechanisms of pyroptosis, highlights the latest progress of pyroptosis in autoimmune skin disease, including systemic lupus erythematosus, psoriasis, atopic dermatitis and systemic scleroderma and attempts to identify its potential advantages as a therapeutic target or prognostic biomarker for these diseases.

The structure and function of multifunctional protein ErbB3 binding protein 1 (Ebp1) and its role in diseases.

ErbB3-binding protein 1(Ebp1) has two isoforms, p42 Ebp1 and p48 Ebp1, both of which can regulate cell growth and differentiation. But these isoforms often have opposite effects, including contradictory roles in regulation of cell growth in different tissues and cells. P48 Ebp1 belongs to the full-length sequence, while conformational changes in the crystal structure of p42 Ebp1 reveals a lack of an α helix at the amino terminus. Due to the differences in the structures of these two isoforms, they have different binding partners and protein modifications. Ebp1 can function as both an oncogene and a tumor suppressor factor. However, the underlying mechanisms by which these two isoforms exert opposite functions are still not fully understood. In this review, we summarize the genes and the structures of protein of these two isoforms, protein modifications, binding partners and the association of different isoforms with diseases.

Mitochondrial GPX4 acetylation is involved in cadmium-induced renal cell ferroptosis.

Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD+-dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3-/- mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.

The link between autophagy and psoriasis.

Autophagy is a lysosome-dependent, self-renewal mechanism that degrades and recycles cellular components in eukaryotic cells to maintain the homeostasis of the intracellular environment. Psoriasis is featured by increased inflammatory response, epidermal hyperproliferation and abnormal differentiation, infiltration of immune cells and increased expression levels of both endothelial adhesion molecules and angiogenic mediators. Evidence indicates that autophagy has important roles in many different types of cells, such as lymphocytes, keratinocytes, monocytes and mesenchymal stem cells (MSCs). This paper will review the role of autophagy in the pathogenesis of psoriasis and strategies for therapeutic modulation. Key Message Autophagy regulates the functions of cutaneous cells (MSCs, KCs, T cells and endothelial cells). Since reduced autophagy contributes in part to the pathogenesis of psoriasis, enhancement of autophagy can be an alternative approach to mitigate psoriasis.

Arsenic exposure causes decline in sperm motility accompanied by energy metabolism disorders in mouse testes.

Arsenic (As) is a notorious environmental toxicant widely present in various natural environments. As exposure has been correlated with the decline in sperm motility. Yet, the mechanism has not been fully elucidated. Adult male C57 mice were given 0, 1, or 15 mg/L NaAsO2 for 10 weeks. The mature seminiferous tubules and sperm count were decreased in As-exposed mice. Sperm motility and several sperm motility parameters, including average path velocity (VAP), straight-line velocity (VSL), curvilinear velocity (VCL), beat-cross frequency (BCF), linearity (LIN), straightness (STR), and amplitude of lateral head displacement (ALH), were declined in As-exposed mice. RNA sequencing and transcriptomics analyses revealed that differentially expressed genes (DEGs) were mainly enriched in metabolic pathways. Untargeted metabolomics analyses indicated that energy metabolism was disrupted in As-exposed mouse testes. Gene set enrichment analysis showed that glycolysis and oxidative phosphorylation were disturbed in As-exposed mouse testes. As-induced disruption of testicular glucose metabolism and oxidative phosphorylation was further validated by RT-PCR and Western blotting. In conclusion, As exposure causes decline in sperm motility accompanied by energy metabolism disorders in mouse testes.

Medical image fusion with deep neural networks.

Medical image fusion aims to fuse multiple images from a single or multiple imaging modes to enhance their corresponding clinical applications in diagnosing and evaluating medical problems, a trend that has attracted increasing attention. However, most recent medical image fusion methods require prior knowledge, making it difficult to select image features. In this paper, we propose a novel deep medical image fusion method based on a deep convolutional neural network (DCNN) for directly learning image features from original images. Specifically, source images are first decomposed by low rank representation to obtain the principal and salient components, respectively. Following that, the deep features are extracted from the decomposed principal components via DCNN and fused by a weighted-average rule. Then, considering the complementary between the salient components obtained by the low rank representation, a simple yet effective sum rule is designed to fuse the salient components. Finally, the fused result is obtained by reconstructing the principal and salient components. The experimental results demonstrate that the proposed method outperforms several state-of-the-art medical image fusion approaches in terms of both objective indices and visual quality.

Design and Realization of Ni Clusters in MoS2@Ni/RGO Catalysts for Alkaline Efficient Hydrogen Evolution Reaction.

Due to their almost zero relative hydrogen atom adsorption-free energy, MoS2-based materials have received substantial study. However, their poor electronic conductivity and limited number of catalytic active sites hinder their widespread use in hydrogen evolution reactions. On the other hand, metal clusters offer numerous active sites. In this study, by loading Ni metal clusters on MoS2 and combining them with the better electrical conductivity of graphene, the overpotential of the hydrogen evolution reaction was reduced from 165 mV to 92 mV at 10 mA·cm-2. This demonstrates that a successful method for effectively designing water decomposition is the use of synergistic interactions resulting from interfacial electron transfer between MoS2 and Ni metal clusters.

Mitoquinone alleviates bleomycin-induced acute lung injury via inhibiting mitochondrial ROS-dependent pulmonary epithelial ferroptosis.

Numerous studies demonstrated that bleomycin (BLM) caused acute lung injury (ALI). This study explored the role of mitochondrial reactive oxygen species (ROS) on BLM-induced ALI and pulmonary epithelial ferroptosis. Male C57BL/6J mice were intratracheally injected with BLM (3.0 mg/kg). BEAS-2B cells, human bronchial epithelial cells, were cultured with BLM (10 µg/ml). Pulmonary MDA and 4-HNE, two markers of lipid peroxidation, were elevated in BLM-exposed mice. Oxidized lipids were upregulated in BLM-exposed BEAS-2B cells. Ferroptosis-characteristic ultrastructure, mainly disappearance of mitochondrial bilayer membrane structure and cristae, was observed in BLM-exposed pulmonary epithelium. Ferrostatin-1, a specific inhibitor of ferroptosis, attenuated BLM-evoked pulmonary lipid peroxidation, ferroptosis-characteristic mitochondrial ultrastructure and pulmonary epithelial death. The in vitro experiments showed that mitochondrial membrane potentials (MMPs) were decreased and mitochondrial ROS were increased in BLM-exposed BEAS-2B cells. Mitoquinone (MitoQ), a mitochondria-targeted antioxidant, prevented BLM-induced MMP reduction and mitochondrial ROS elevation in BEAS-2B cells. The in vivo experiment found that MitoQ attenuated BLM-evoked GSH depletion and lipid peroxidation in mouse lungs. Moreover, MitoQ prevented BLM-induced ferroptosis-characteristic mitochondrial changes, pulmonary epithelial death and ALI. In conclusion, mitochondrial ROS are an initiator of BLM-induced pulmonary epithelial ferroptosis. Mitochondria-targeted antioxidants may be used as potential therapeutic agents for BLM-induced ALI.

Fe3O4/Diatomite-Decorated Cotton Evaporator for Continuous Solar Steam Generation and Water Treatment.

Improving the evaporation rate of solar steam generation (SSG) has always been a research hotspot to solve the shortage of water resources. Using cotton, Fe3O4, polyvinyl alcohol (PVA) and diatomite (DM) as raw materials, DM/PVA/Fe3O4@cotton composites with both firmness and hydrophilicity were prepared. Fe3O4 has a wide range of light absorption characteristics and good photothermal conversion performance, and is an ideal photothermal conversion material. PVA enhances the adhesion between Fe3O4, cotton and DM and enhances the hardness of the sample and the internal porous structure. The existence of DM greatly improves the hydrophilicity of the sample, ensuring that the water in the lower layer can be continuously transported to the surface of the sample, and DM makes the surface of the sample rough, which reduces the reflection of sunlight and improves the efficiency of light heat conversion. Under one-sun irradiation, the temperature of the sample surface increases by 52.6 °C, the evaporation rate can reach 1.32 kg m-2 h-1 and the evaporation efficiency is 82.9%. Using this sample as the photothermal conversion layer of the SSG device, the removal rate of salt ions in seawater is more than 98% and the removal rate of heavy metal ions in sewage is close to 100%. This work provides a new idea and design method for SSG in the field of seawater desalination and sewage treatment.

Normal mesenchymal stem cells can improve the abnormal function of T cells in psoriasis via upregulating transforming growth factor-ß receptor.

Psoriasis, a chronic inflammatory skin disease, is a refractory disorder. Previous studies have shown that the imbalance of the T-helper (Th)17/regulatory T cells (Treg) results in the immune imbalance of T cells in psoriatic patients, and that mesenchymal stem cells display an immunosuppressive role by promoting the differentiation of T cells into Treg, leading to a reduction in the proportion of Th17/Treg. Utility of mesenchymal stem cells is becoming a new approach for the treatment of immune disorders. Following co-culture of dermal mesenchymal stromal cells (DMSC) and CD3+ T cells with or without transforming growth factor (TGF)-ß receptor inhibitor, the biological function and relative signal pathway of CD3+ T cells were assessed by flow cytometry, transwell, real-time polymerase chain reaction and western blotting, respectively. Normal DMSC were more potent than psoriatic DMSC in inhibition of CD3+ T-cell proliferation, and stimulation of CD3+ T-cell apoptosis than psoriasis DMSC. Moreover, normal DMSC decreased the ratio of Th17/Treg, while enhancing the immunosuppressive effect of Tregs on effector T cells. However, TGF-ß receptor (TGF-ßR) inhibitor attenuated the effect of normal DMSC on CD3+ T cells and Th17/Treg ratio. Additionally, the normal DMSC were more potent than the psoriatic DMSC in increasing TGF-ß receptors and activation of TGF-ß/SMAD pathway in psoriatic CD3+ T cells. In conclusion, normal DMSC can partially improve the biological function and immunosuppressive ability of psoriatic CD3+ T cells, possibly via upregulating the TGF-ß receptors.

Mitochondria-derived reactive oxygen species are involved in renal cell ferroptosis during lipopolysaccharide-induced acute kidney injury.

Our earlier studies indicated that reactive oxygen species (ROS) were involved in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). The present study aimed to explore the role of mitochondria-derived ROS on renal cell ferroptosis during LPS-induced AKI. Male CD-1 mice were intraperitoneally injected with LPS (2.0 mg/kg). Renal MDA and 4HNE residue, two markers of lipid peroxidation, were increased in LPS-exposed mice. Oxidized lipids were detected in LPS-treated human HK-2 cells. In vivo, ferroptosis-characteristic ultrastructure changes, including cell volume reduction, nuclear pyknosis and smaller mitochondria, were shown in renal cortex. In vitro, abnormal alteration of mitochondrial membrane potential was observed in LPS-treated human HK-2 cells. Ferrostatin-1, a specific inhibitor of ferroptosis, attenuated LPS-evoked renal lipid peroxidation, ferroptosis-characteristic mitochondrial damage and renal cell death. Mechanistically, mitochondria-derived ROS were elevated in LPS-stimulated HK-2 cells. MitoQ, a mitochondria-targeted antioxidant, almost completely scavenged LPS-stimulated mitochondrial ROS in human HK-2 cells. Moreover, pretreatment with MitoQ attenuated LPS-induced GSH depletion and lipid peroxidation in mouse kidney. Finally, pretreatment with MitoQ alleviated LPS-induced renal cell death and AKI. Taken together, these results suggest that mitochondria-derived ROS contribute, at least partially, to renal cell ferroptosis during LPS-induced AKI. Mitochondria-targeted antioxidants may be potential therapeutic agents for sepsis-induced AKI.

Dermal Mesenchymal Stem Cells from Psoriatic Lesions Stimulate HaCaT Cell Proliferation, Differentiation, and Migration via Activating the PI3K/AKT Signaling Pathway.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal differentiation of keratinocytes. Dermal mesenchymal stem cells (DMSCs) are not only involved in the regeneration of skin tissue, but also can regulate skin microenvironment by secreting cytokines. However, whether and how psoriatic DMSCs regulate proliferation and differentiation of keratinocytes remains unknown. OBJECTIVE: To study the effects of psoriatic DMSCs on the proliferation, differentiation, and migration of keratinocytes and the underlying mechanisms. METHODS: Following co-cultures of HaCaT cells with either psoriatic DMSCs (p-DMSCs) or DMSCs from normal volunteers (n-DMSCs), HaCaT cell proliferation was assessed using CCK-8 and EDU incorporation assay, while scratch assay and transwell assay were used to assess cell migration. qRT-PCR was used to determine expression levels of mRNA for cell proliferation (Ki-67) and differentiation (keratin 5, involucrin, and filaggrin). Western blot was used to measure expression levels of proteins associated with keratinocyte proliferation and differentiation in cultured HaCaT cells treated with or without PI3K inhibitor. ELISA assay was used to measure expression profile of stem cell factor (SCF), epidermal growth factor (EGF), and interleukin-11 (IL-11) within the co-culture supernatants. RESULTS: The results showed that p-DMSCs displayed a higher potency than n-DMSCs in stimulating proliferation, differentiation, and migration of HaCaT cells. Expression levels of PI3K and AKT proteins were markedly increased in HaCaT cells co-cultured with DMSCs versus HaCaT cell culture alone. Moreover, inhibition of the PI3K/AKT signaling pathway reversed the effect of p-DMSCs on proliferation, differentiation, and migration of HaCaT cells. Compared with n-DMSCs, the p-DMSCs showed increased secretion of IL-11, EGF, and SCF. CONCLUSION: p-DMSCs stimulate HaCaT cell proliferation, differentiation and migration via activating the PI3K/AKT signaling pathway, providing a new insight into the pathogenesis of psoriasis.

Role of psoriatic keratinocytes in the metabolic reprogramming of dermal mesenchymal stem cells.

BACKGROUND: Psoriasis is an immune-mediated inflammatory skin disease, featured by epidermal hyperproliferation. Psoriasis exhibits metabolic abnormalities, which can further aggravate the condition of psoriasis. The present study aimed to investigate the role of psoriatic keratinocytes (KCs) in the metabolic reprogramming of dermal mesenchymal stem cells (DMSCs). METHODS: Dermal mesenchymal stem cells were cocultured with primary KCs either from psoriatic lesions or from normal subjects using Transwell plate. Glycolysis and mitochondrial metabolism of DMSCs were detected by Seahorse Metabolic Analyzer. Expression levels of proteins were analyzed by Western blotting. DMSCs proliferation was assessed using 5-ethynyl-2'-deoxyuridine assay and Cell Counting Kit-8. RESULTS: In comparison with normal KCs, coculture of psoriatic KCs with DMSCs dramatically increased glycolytic and mitochondrial metabolism, and expression levels of stem cell factor, epidermal growth factor, glucose transporter 1, and c-Myc. Moreover, psoriatic KCs were more potent than normal KCs in the stimulation of DMSC proliferation. CONCLUSIONS: In conclusion, psoriatic KCs display a higher potency in metabolic reprogramming and stimulation of DMSC proliferation, possibly contributing to the pathogenesis of psoriasis. However, whether the intervention of metabolic reprogramming of DMSCs can alleviate psoriasis remains to be determined.

Functional differentiation related to decomposing complex carbohydrates of intestinal microbes between two wild zokor species based on 16SrRNA sequences.

BACKGROUND: The intestinal microbes in mammals play a key role in host metabolism and adaptation. As a subterranean rodent, zokor digs tunnels for foraging and mating. These digging activities of zokors increase the energy expenditure relative to their aboveground counterparts. However, relatively little is known regarding intestinal microbes of zokor and how they make full use of limited food resources underground for high energy requirements. RESULTS: Eospalax cansus and Eospalax rothschildi had distinct intestinal microbes. Although the composition of intestinal microbes is similar in two species, the proportion of bacterium are distinctly different between them. At phylum level, 11 phyla were shared between two species. Firmicutes and Bacteroidota were two dominant microbes in both of two species, while Eospalax cansus have a significantly high proportion of Firmicutes/Bacteroidota than that of Eospalax rothschildi. At genus level, norank_f_Muribaculaceae were dominant microbes in both of two zokor species. The relative abundance of 12 genera were significantly different between two species. Some bacterium including unclassified_f__Lachnospiraceae, Lachnospiraceae_NK4A136_group, Ruminococcus and Eubacterium_siraeum_group associated with cellulose degradation were significantly enriched in Eospalax cansus. Although alpha diversity was with no significant differences between Eospalax cansus and Eospalax rothschildi, the intestinal microbes between them are significant distinct in PCoA analysis. We have found that trapping location affected the alpha diversity values, while sex and body measurements had no effect on alpha diversity values. PICRUSt metagenome predictions revealed significant enrichment of microbial genes involved in carbohydrate metabolism in Eospalax cansus rather than Eospalax rothschildi. CONCLUSIONS: Our results demonstrate that Eospalax cansus harbor a stronger ability of fermentation for dietary plants than Eospalax rothschildi. The stronger ability of fermentation and degradation of cellulose of intestinal microbes of Eospalax cansus may be a long-time adaptation to limited food resources underground.

The effects of human dermal-derived mesenchymal stem cells on the keratinocyte proliferation and apoptosis in psoriasis.

Psoriasis is a common chronic inflammatory skin disease, characterized by epidermal hyperproliferation. Mesenchymal stem cells (MSCs) regulate inflammation and vascular proliferation in the psoriasis lesions. Whether dermal-derived mesenchymal stem cells (DMSCs), the main MSCs in the dermis, regulate keratinocyte proliferation and apoptosis remains unknown. In the present study, we assessed the proliferation and apoptosis of keratinocytes cocultured with DMSCs isolated from either normal or psoriatic involved skin. Cell growth and apoptotic rates were determined using Cell Count Kit-8 and annexin V-FITC staining, respectively. In addition, EDU kit was also used to measure the rate of keratinocyte proliferation. Our results showed that psoriatic DMSCs (pDMSCs) were more potent than normal DMSCs (nDMSCs) in stimulating keratinocyte proliferation. In contrast, the apoptotic rate and expression levels of caspase-3 protein were lower in pDMSC-treated than nDMSC-treated keratinocytes (p < 0.001). Moreover, significantly higher contents of IL-6, IL-8, TNF-α and IFN-γ were found in the culture medium of pDMSCs than in that of nDMSCs. In conclusion, pDMSCs were more potent than nDMSCs in stimulation of keratinocyte proliferation and secretion of proinflammatory cytokines, but weaker in promoting apoptosis.

Oxidation Behaviors of Aluminum Nanopowders with Different Particle Sizes: A Real-Time Synchrotron X-ray Scattering Study.

We have studied the oxidation behaviors of aluminum (Al) nanopowders with different particle sizes using a real-time synchrotron X-ray scattering during annealing in air. The Al nanopowders with small particle size of 78 nm at room temperature (RT) were a single crystal. The surface of the nanopowders was first oxidized to amorphous Al oxide near 450 °C, and then crystallized to γ-Al2O3 phase at 550 °C. The inside of the nanopowders existed as crystal Al phase at 680 °C, high compared to the melting temperature of Al bulk, 660 °C. In contrast, the Al nanopowders with large particle size of 816 nm at RT have multi grains inside a particle. The surface and grain boundary of the powders were first oxidized to amorphous Al oxide near 470 °C, and then crystallized to γ-Al2O3 phase at 550 °C. The inside of the powders existed as amorphous Al phase at 620 °C, melted at 656 °C, and then oxidized gradually above 656 °C.

Annealing Behaviors of Al and Al-Mg-Si Alloy: A Real-Time Synchrotron X-ray Scattering Study.

We have studied the annealing behaviors of pure Al (Al-1050) and Al-Mg-Si alloy (Al-6061) with plate-type using a real-time synchrotron X-ray scattering in vacuum. At room temperature (RT), the crystal domain size of Al phase in the Al-Mg-Si alloy was small as 70 nm, compared to that in the pure Al, 142 nm. The crystal Al phase in the Al-Mg-Si alloy has more thermal stability than that in the pure Al. The crystal Al phase in the Al-Mg-Si alloy was thermally stable in amount and size up to 250 °C. These are due to the existence of intermetallic crystal Mg2Si phase, which is thermally stable in amount and size up to 250 °C.

The regulation of dermal mesenchymal stem cells on keratinocytes apoptosis.

Dermal mesenchymal stem cells (DMSCs) are progenitor cells with the capacity of self-renewal, multilineage differentiation, and immunomodulation, which were reported to induce the proliferation of keratinocytes, however the regulation on keratinocytes apoptosis was unknown. In this study, we isolated DMSCs from normal skin and co-cultured with keratinocytes, and then detected apoptosis of keratinocytes by flow cytometry and expression of apoptosis associated proteins by western blot. The mRNA expression profile of normal DMSCs was investigated by RNA sequencing. The results of our study presented that the DMSCs promoted HaCaT cells apoptosis both in early apoptotic state (13.8 vs. 2.9, p < 0.05) and late apoptotic state (4.2 vs. 0.7, p < 0.05). The expression of apoptosis associated proteins caspase-3 (3.51 vs. 1.99, p < 0.05) and lymphoid enhancer-binding factor 1 (3.10 vs. 0.83, p < 0.05) were upregulated. However, the cell cycle protein cyclin E1 was similar (9.38 vs. 9.05, p > 0.05). Moreover, 33 genes with the function of induced cell apoptosis were highly expressed in DMSCs, including insulin-like growth factor-binding protein 4 (2828.13), IGFBP7 (1805.69), cathepsin D (1694.34), cathepsin B (CTSB, 1641.40) and dickkopf WNT signaling pathway inhibitor 1 (DKK1, 384.79). This study suggested DMSCs induce the apoptosis of keratinocytes through non-G1/S phase blockade via highly expression of apoptosis inducer.

Taxonomy and phylogenetic relationship of zokors.

Zokor (Myospalacinae) is one of the subterranean rodents, endemic to east Asia. Due to the convergent and parallel evolution induced by its special lifestyles, the controversies in morphological classification of zokor appeared at the level of family and genus. To resolve these controversies about taxonomy and phylogeny, the phylogenetic relationships of 20 species of Muroidea and six species of zokors were studied based on complete mitochondrial genome and mitochondrial Cytb gene, respectively. Phylogeny analysis of 20 species of Muroidea indicated that the zokor belonged to the family Spalacidae, and it was closer to mole rat rather than bamboo rat. Besides, by investigating the phylogenetic relationships of six species of zokors, the status of two genera of Eospalax and Myospalax was affirmed because the two clades differentiated in phylogenetic tree represented two types of zokors, convex occiput type and flat occiput type, respectively. In addition, the two origins in Eospalax were found diverged at 3.71 million years ago (Ma) based on estimation of divergence time. It is suggested that the climate and ecology changes caused by the Qinghai-Tibet Plateau uplift event in 3.6 Ma led to the inner divergence of Eospalax. The intraspecific phylogenetic relationships of partial zokors were well resolved, the two clades of Eospalax cansus represented two geographical populations, respectively, and the divergent pattern of Eospalax baileyi was characterized by allopatric divergence spatially. In this study, we explored the taxonomic status and phylogenetic relationships of Myospalacinae at the molecular level. These works would be significant to understanding the evolutionary process and to clarify the mechanism of differentiation of Myospalacinae.